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1.
São Paulo; s.n; s.n; 2024. 138 p tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1565955

ABSTRACT

Este trabalho teve como objetivo o estudo dos possíveis substitutos da sacarose em chocolates. O trabalho foi dividido em três capítulos a fim de se realizar um estudo abrangente sobre o tema. No Capítulo 1, concluiu-se, através de uma revisão bibliográfica, que a qualidade da textura e a estabilidade do chocolate são significativamente influenciadas pela existência de cristais específicos, especialmente os provenientes do açúcar. Por essa razão, é crucial examinar cuidadosamente a substituição desse componente. A literatura estudada menciona diversos edulcorantes e espessantes empregados para substituir a sacarose em chocolates, como os edulcorantes nutritivos e não-nutritivos, assim como os espessantes mais aplicados. O melhor edulcorante e fibra, considerando-se as literaturas estudadas, em termos de custo, propriedades reológicas e mouthfeel, para a substituição da sacarose em chocolates, seria o maltitol e a polidextrose. No Capítulo 2, foram comparados alguns chocolates amargos e ao leite, com e sem sacarose presentes no mercado. Estes chocolates apresentaram comportamento calorimétrico indicando pico de fusão, pico de caramelização e pico de carbonização variáveis de acordo com a formulação. Os chocolates apresentaram forças de ruptura semelhantes, entretanto, o dimensional das amostras influenciou na textura dos produtos. O tipo de edulcorante e os ingredientes utilizados, influenciaram no fluxo de escoamento e nas características físicas, como a cor dos chocolates. No Capítulo 3, foram formulados dois chocolates amargos, um com adição de açúcar e um com a adição de uma mistura comercial (contendo fibra de mandioca/tapioca e edulcorantes), disponível comercialmente, porém sem estudos anteriores de aplicação em chocolates, em substituição à sacarose. As amostras foram comparadas, entre si e em relação aos valores encontrados na literatura, quanto as suas propriedades nutricionais, físico-químicas e reológicas. A substituição da sacarose, pela mistura comercial, demonstrou comportamento próximo das amostras de mercado estudadas no Capítulo 2. Concluiu-se que a mistura comercial cumpre as funções da sacarose em formulação de chocolate amargo diet, mesmo que alterando algumas das propriedades físico-químicas e reológicas. Entretanto, esta mistura não é indicada para uso em formulações de chocolates forneáveis, pois apresenta pico de carbonização em temperatura precoce


This work aimed to study possible sucrose substitutes in chocolates. The study was divided into three chapters to conduct a comprehensive examination of the topic. In Chapter 1, it was concluded, through a literature review, that the texture quality and stability of chocolate are significantly influenced by the presence of specific crystals, especially those derived from sugar. For this reason, it is crucial to carefully examine the replacement of this component. The literature studied mentions various sweeteners and thickeners used to replace sucrose in chocolates, including both nutritive and non-nutritive sweeteners, as well as commonly applied thickeners. According to the literature reviewed, the best sweetener and fiber for the replacement of sucrose in chocolates, considering cost, rheological properties, and mouthfeel, would be maltitol and polydextrose. In Chapter 2, some dark and milk chocolates without sucrose available in the market were compared. These chocolates exhibited calorimetric behavior indicating variable melting peaks, caramelization peaks, and carbonization peaks according to the formulation. The chocolates exhibited similar breaking strengths, however, the dimensional characteristics of the samples influenced the texture of the products. The type of sweetener and ingredients used influenced the flow behavior and physical characteristics, such as the color of the chocolates. In the Chapter 3, two dark chocolates were formulated, one with sugar added and one with the addition of a commercial blend (containing cassava/tapioca fiber and sweeteners), commercially available, but without previous studies of application in chocolates, as a substitute for sucrose. The samples were compared, both between themselves and in relation to the values found in the literature, regarding its nutritional, physicochemical, and rheological properties. The replacement of sucrose with the commercial blend demonstrated behavior similar to the market samples studied in Chapter 2. It is concluded that the commercial blend fulfills the functions of sucrose in diet dark chocolate formulation, even changing some of the physicochemical and rheological properties of the chocolate. However, this blend is not recommended for the use in bakeable chocolate formulations, as it exhibits an early peak of carbonization


Subject(s)
Sucrose/agonists , Sweetening Agents/adverse effects , Chocolate/analysis , Caloric Restriction/classification , Differential Thermal Analysis/methods , Diet, Food, and Nutrition
2.
Eur J Pharm Biopharm ; 169: 125-133, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34655768

ABSTRACT

Understanding drug miscibility in pharmaceutically relevant systems is essential for the development and optimisation of pharmaceutical dosage forms. This is particularly true for film forming systems which are designed to become supersaturated with drug, following application on the skin surface, whilst maintaining the physical stability of the drug for a suitable period to enhance drug delivery. For such formulations, chemical penetration enhancers as well as the drug are absorbed from the formulation into the skin, making understanding drug delivery from the films challenging. This study investigated the use of an optical differential scanning calorimetry (DSC) to understand drug miscibility in polymeric film forming systems and explain drug transport behaviour from film forming formulations, containing ibuprofen, a copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate (Eudragit® E, EuE), a copolymer based on ethyl acrylate, methyl methacrylate and methacrylic acid ester with quaternary ammonium groups (Eudragit® RS, EuRS) and a copolymer based on methacrylic acid and methyl methacrylate (Eudragit® S, EuS), with and without the chemical penetration enhancer propylene glycol, across a model membrane. The optical DSC enabled the rapid screening of not only drug-polymer miscibility, but also drug-vehicle miscibility, while considering both the melting-point depression and melting enthalpy of the drug due to the presence of the polymer/polymer-based vehicle, obtained via thermal analysis by structural characterisation (TASC) and DSC analysis, respectively. The results obtained enable the polymers studied to be ranked in the order of EuE > EuRS > EuS, with EuE being more miscible with ibuprofen, and the incorporation of a penetration enhancer in the film forming system formulation was found to increase ibuprofen solubility in EuE- and EuRS- based films. The drug-polymer/vehicle miscibility information obtained via optical DSC provided understanding of drug transport from film forming systems with the higher miscibility of ibuprofen with EuE reducing drug transport through decreasing drug saturation in the film. The higher drug transport from films containing EuRS and EuS could also be linked to drug miscibility with the polymer and showed dependence on ibuprofen loading in the formulation. Overall optical DSC has been demonstrated to be a valuable tool for determining drug-vehicle miscibility for pharmaceutical product development.


Subject(s)
Calorimetry, Differential Scanning/methods , Drug Delivery Systems/methods , Ibuprofen/pharmacology , Polymethacrylic Acids/pharmacology , Administration, Topical , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Chemistry, Pharmaceutical/methods , Differential Thermal Analysis/methods , Drug Compounding/methods , Drug Liberation , Humans , Skin Absorption/drug effects , Solubility
3.
Methods Mol Biol ; 2156: 23-31, 2020.
Article in English | MEDLINE | ID: mdl-32607972

ABSTRACT

Frost tolerance is an important factor influencing plant growth, plant species distribution and competitive balance among plant species in the face of climate change. Traditional methods for estimating frost tolerance are often time consuming and require a large sample size, limiting the temporal and spatial resolutions. Differential thermal analysis (DTA) can be advantageous compared to other methods used to determine frost tolerance, most importantly by (1) increasing the number of tested species, tissue types and sampling dates, (2) allowing to test frost tolerance in situ, and (3) more realistically testing the influence of freezing rate and duration. Here, we discuss a typical procedure for DTA, compare its use to other frost tolerance methods and point out its limitations.


Subject(s)
Adaptation, Biological , Differential Thermal Analysis , Freezing , Plant Physiological Phenomena , Seasons , Differential Thermal Analysis/methods , Organ Specificity , Phenotype
4.
Methods Mol Biol ; 2156: 33-41, 2020.
Article in English | MEDLINE | ID: mdl-32607973

ABSTRACT

Infrared thermal analysis is an invaluable technique to study the plant freezing process. In the differential mode, infrared thermal analysis (IDTA) allows to localize ice nucleation and ice propagation in whole plants or plant samples at the tissue level. Ice barriers can be visualized and supercooling of cells, tissues, and organs can be monitored. Places where ice masses are accommodated in the apoplast can be identified. Here, we describe an experimental setting developed in our laboratory, give detailed information on the practical procedure and preconditions, and give additionally an idea of the problems that would be encountered and how they may be overcome.


Subject(s)
Differential Thermal Analysis , Freezing , Plant Physiological Phenomena , Spectrophotometry, Infrared , Data Analysis , Differential Thermal Analysis/methods , Plant Leaves/physiology , Spectrophotometry, Infrared/methods
5.
J Pharm Biomed Anal ; 181: 113065, 2020 Mar 20.
Article in English | MEDLINE | ID: mdl-32032919

ABSTRACT

Thermal shift assay is a fluorescence dye based biochemical method to determine the melting point of a protein. It can be used to investigate the ligand-induced stabilization of proteins and helps to increase the likelihood of crystallization in biological samples. Dimeric proteins like soluble guanylyl cyclase (sGC) have specific structural and functional properties which may pose a challenge in thermal shift measurements. In this paper, thermal shift assay was used to examine ligand-induced thermostabilization of the dimeric heme-containing protein soluble guanylyl cyclase. Adjustment of the parameters buffer solution, pH, protein / dye ratio and protein amount per well yielded a one-phase melting curve of sGC with a sharp transition and high reproducibility. We found that thermal shift measurement is not affected by heme state or heme content of the enzyme preparation. We used the method to investigate the thermostabilization of sGC induced by the heme-mimetic activator drugs cinaciguat, BAY 60-2770 and BR 11257 in combination with non-hydrolyzable nucleotides. Measurements with the dicarboxylic drugs cinaciguat and BAY 60-2770 yielded steep melting curves with high amplitudes. In contrast, in the presence of the monocarboxylic sGC activator BR 11257, melting curves appear flattened in the dye-based measurements. In the present paper, we show that activity-based thermostability measurements are superior to dye-based measurements in detecting the thermostabilizing influence of sGC activator drugs.


Subject(s)
Differential Thermal Analysis/methods , Enzyme Stability/drug effects , Soluble Guanylyl Cyclase/chemistry , Benzoates/pharmacology , Biphenyl Compounds/pharmacology , Hydrocarbons, Fluorinated/pharmacology , Ligands , Nucleotides/pharmacology , Transition Temperature
6.
Cryobiology ; 91: 128-136, 2019 12.
Article in English | MEDLINE | ID: mdl-31526802

ABSTRACT

This study aims at the thermal analysis of marginal conditions leading to cryopreservation by vitrification, which appears to be the only alternative for indefinite preservation of large-size tissues and organs. The term "marginal conditions" here refers to cooling rates in close range with the so-called critical cooling rate, above which crystallization is avoided. The analysis of thermal effects associated with partial crystallization during vitrification is associated with the coupled phenomena of heat transfer and kinetics of crystallization. This study takes a practical, semi-empirical approach, where heat transfer is analyzed based on its underlying theoretical principles, while the thermal effects associated with partial crystallization are taken into account by means of empirical correlations. This study presents a computation framework to solve the coupled problem, while presenting a proof-of-concept for DP6 as a representative cryoprotective agent. The thermal effects associated with crystallization at various relevant cooling rates are measured in this study by means of differential scanning calorimetry. Results of this study demonstrate that, due to the thermal effects associated with partial crystallization, the cooling rate at the center of a large organ may lag behind the cooling rate in its surroundings under some scenarios, but may also exceed the surroundings cooling rate in other scenarios, leading to counter-intuitive effects associated with partial crystallization.


Subject(s)
Calorimetry, Differential Scanning/methods , Cryopreservation/methods , Cryoprotective Agents/pharmacology , Differential Thermal Analysis/methods , Dimethyl Sulfoxide/pharmacology , HEPES/pharmacology , Organ Preservation/methods , Propylene Glycols/pharmacology , Cold Temperature , Cryoprotective Agents/chemistry , Crystallization , Hot Temperature , Phase Transition , Vitrification
7.
Skin Res Technol ; 25(2): 150-157, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30112768

ABSTRACT

BACKGROUND: Hyaluronic acid (HA) has been considered the gold standard ingredient for improving skin hydration and combating age-related effects, however it is an inefficient polymer with inconsistent results partially due to its poor skin penetration, surface deposition, and rapid degradation. Herein we report the synthesis and in vitro characterization of a newly developed, topical super-humectant with the goal of attracting and binding water molecules more efficiently than traditional, cosmetic-grade forms of HA. METHODS: A modified interpenetrating polymer network (IPN) was developed using three polymers into a three-dimensional formation (3D3P) for entrapping HA and water. This 3D3P-IPN functions as a super-humectant, attracting and binding water molecules more efficiently than the traditional cosmetic-grade forms of HA. We compare 3D3P-IPN serum samples to a traditional commercial benchmark product of similar ingredients using microscopic analysis, rheology, Karl Fischer (KF) titration, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), and dynamic vapor sorption (DVS) techniques. RESULTS: The 3D3P-IPN samples appeared to bind water tighter than the benchmark sample as evidenced by maximum endpoints of endotherms occurring at significantly higher temperatures. The DVS results further confirm this speculation as the 3D3P-IPN samples lost approximately 10% less water up to 35% RH than the benchmark. The 3D3P-IPN samples also absorbed more water as the humidity level increased,demonstrating superior humectant properties. KF titration indicated that all three samples had similar water concentrations; however, TGA results demonstrated that the benchmark (a viscous, humectant-rich hydrating masque) did not have much bound water. CONCLUSION: Through the synthesis of a 3D3P-IPN using simplified methods, we were able to increase the water-binding and HA-delivery capabilities of a thin serum. This 3D3P-IPN serum has potential to deliver more hydration to the skin's surface compared to traditional HA formulations.


Subject(s)
Hyaluronic Acid/chemistry , Molecular Imprinting/methods , Polymers/analysis , Skin/metabolism , Water/chemistry , Calorimetry, Differential Scanning/methods , Differential Thermal Analysis/methods , Drug Compounding/trends , Humans , Models, Theoretical , Organism Hydration Status/drug effects , Rheology/drug effects , Skin Absorption/physiology , Skin Physiological Phenomena , Temperature , Water/metabolism
8.
Mol Pharm ; 15(12): 5625-5636, 2018 12 03.
Article in English | MEDLINE | ID: mdl-30372612

ABSTRACT

This study aimed to develop a rapid, simple, and inexpensive screening method for selecting the best polymeric candidates possessing high active pharmaceutical ingredient (API) miscibility during the early stages of formulation development of solid dispersion based pharmaceutical products. A new thermal imaging based method, thermal analysis by structural characterization (TASC), was used as a thermoptometric tool in conjunction with data analysis software to detect the melting point depression and postmelting dissolution of felodipine particles screened over thin spin-coated films of ten polymers commonly used in the pharmaceutical field. On the polymeric substrates the drug showed different degrees of melting point reduction, reflecting their different levels of polymer-drug miscibility. Using TASC to detect melting point depression is significantly (20-40 times) faster than the conventional DSC method without loss of the sensitivity of detection. The quantity of the material required for the screening is less than 1/1000th of the material used in conventional DSC tests, which significantly reduce the material wastage. Isothermal TASC tests and IR imaging confirmed the occurrence of thermal dissolution of the drug in the polymer for more miscible pairs. The real-time stability tests validate the accuracy of the polymer-drug miscibility screening results. These results demonstrate TASC as a promising screening tool for rapidly selecting the polymeric excipients for pharmaceutical formulations development.


Subject(s)
Differential Thermal Analysis/methods , Drug Compounding/methods , Excipients/chemistry , Felodipine/chemistry , Calorimetry, Differential Scanning/methods , Chemistry, Pharmaceutical/methods , Crystallization , Drug Stability , High-Throughput Screening Assays/methods , Molecular Structure , Polymers/chemistry , Solubility
9.
Int J Pharm ; 534(1-2): 119-127, 2017 Dec 20.
Article in English | MEDLINE | ID: mdl-29030289

ABSTRACT

Thermal properties of powders are critical material attributes that control temperature rise during tableting and roll compaction. In this study, various analytical methods were used to measure the thermal properties of widely used pharmaceutical excipients including microcrystalline cellulose (MCC) of three different grades (Avicel PH 101; Avicel PH 102 and Avicel DG), lactose and mannitol. The effect of relative density on the measured thermal properties was investigated by compressing the powders into specimen of different relative densities. Differential thermal analysis (DTA) was employed to explore endothermic or exothermic events in the temperature range endured during typical pharmaceutical manufacturing processes, such as tabletting and roll compaction. Thermogravimetric analysis (TGA) was performed to analyse the water/solvent content, either in the form as solvates or as loosely bound molecules on the particle surface. Thermal conductivity analysis (TCA) was conducted to measure thermal conductivity and volumetric heat capacity. It is shown that, for the MCC powders, almost no changes in morphology or structural changes were observed during heating to temperatures up to 200°C. An increase in relative density or temperature leads to a high thermal conductivity and the volumetric heat capacity. Among all MCC powders considered, Avicel DG showed the highest increase in thermal conductivity and the volumetric heat capacity, but this heat capacity was not sensitive to the measurement temperature. For lactose and mannitol, some endothermic events occurred during heating. The thermal conductivity increased with the increase in temperature and relative density. A model was also developed to describe the variation of the thermal conductivity and the volumetric heat capacity with the relative density and the temperature. It was shown that the empirical model can well predict the dependency of the thermal conductivity and the volumetric heat capacity on the relative density and the temperature.


Subject(s)
Excipients/chemistry , Cellulose/chemistry , Differential Thermal Analysis/methods , Lactose/chemistry , Mannitol/chemistry , Powders/chemistry , Solvents/chemistry , Tablets/chemistry , Temperature , Thermogravimetry/methods , Water/chemistry
10.
Homeopathy ; 106(3): 160-170, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28844289

ABSTRACT

BACKGROUND: A series of different experimental approaches was applied in Zincum metallicum (Zinc met.) samples and lactose controls. Experiments were designed to elucidate the effect of zinc trituration and dynamization on physicochemical properties of homeopathic formulations, using lactose as excipient. METHODS: Zinc met. potencies (Zinc met 1-3c) were triturated and dynamized using lactose as excipient, according to Brazilian Homeopathic Pharmacopoeia. Lactose samples (LAC 1-3c) were also prepared following the same protocol and used as controls. The samples were analyzed structurally by Atomic Absorption Spectroscopy (AAS), X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM) with Energy Dispersive X-ray Spectroscopy (EDX) and Scanning Electron Microscopy (SEM), and thermodynamically by Thermogravimetry (TG) and Differential Scanning Calorimetry (DSC). RESULTS: AAS analysis detected 97.0 % of zinc in the raw material, 0.75 % (Zinc met 1c) and 0.02% (Zinc met 2c). XRD analysis showed that inter-atomic crystalline spacing of lactose was not modified by dynamization. Amorphous and crystalline lactose spheres and particles, respectively, were observed by TEM in all samples, with mean size from 200 to 800 nm. EDX obtained with TEM identified zinc presence throughout the amorphous matter but individualized zinc particles were not observed. SEM images obtained from dynamized samples (LAC 1c and Zinc met 1c) with electron backscattering could not identify zinc metal grains. The dynamization process induced Derivatives of Thermal Gravimetric (DTg) peak modification, which was previously centered near 158°C to lactose, to a range from 140 to 170°C, suggesting the dynamization process modifies the temperature range of water aggregation. Thermal phenomena were analyzed and visualized by Analysis of Variance (ANOVA) and Principal Component Analysis (PCA) statistics. Both indicated that fusion enthalpy of dynamized samples (DynLAC 1-3c; DynZn 1-3c) increased 30.68 J/g in comparison to non-dynamized lactose (LAC; p < 0.05). CONCLUSIONS: Our results suggested no structural changes due to the trituration and dynamization process. However, TG and DSC analyses permit the differentiation of dynamized and non-dynamized groups, suggesting the dynamization process induced a significant increase in the degradation heat. These results call for further calorimetric studies with other homeopathic dilutions and other methodologies, to better understand the dynamics of these systems.


Subject(s)
Differential Thermal Analysis/methods , Homeopathy/methods , Lactose/analysis , Zinc/analysis , Humans , Microscopy, Electron, Transmission/methods , Spectrometry, X-Ray Emission/methods
11.
J Pharm Sci ; 106(3): 826-834, 2017 03.
Article in English | MEDLINE | ID: mdl-27989367

ABSTRACT

Four new solvatomorphs of betulin were reported and characterized by X-ray diffractometry as well as thermal and vibrational spectroscopic analyses. Single-crystal X-ray diffraction was used to analyze the X-ray structures of the compounds and confirmed the stoichiometric ratio between the host and guest molecules from thermal data. Results indicated that solvatomorphism occurred in several betulin solvates. Changes in intermolecular arrangements, stoichiometry, and hydrogen-bonding interactions of solvatomorphs were due to solvent incorporation to solvates. Hirshfeld surface analyses, especially dnorm surface and fingerprint plots, were used to determine intermolecular interactions in the crystal network. Solvent molecules played an important role in the construction of a 3D architecture. The stabilities of these solvates were evaluated by thermal analyses. Nonisothermal kinetic analysis was used to explain the kinetics of solid-solid phase transition (desolvation) of betulin solvates. The apparent activation energies were evaluated using Kissinger and Ozawa methods. Moreover, phase transitions were visually investigated by hot-stage microscopic analysis.


Subject(s)
Differential Thermal Analysis/methods , Models, Chemical , Solvents/analysis , Solvents/chemistry , X-Ray Diffraction/methods , Crystallization/methods , Crystallography, X-Ray/methods , Thermogravimetry/methods
12.
J Pharm Sci ; 106(4): 1062-1068, 2017 04.
Article in English | MEDLINE | ID: mdl-28007560

ABSTRACT

In this study, the effects of structurally related organic impurities on the molecular dynamics of amorphous sulfamethazine were evaluated using thermal analysis. Sulfanilamide (SNA), sulfamerazine (SMR), and sulfadimethoxine were used as virtual impurities of sulfamethazine. The amorphous state was prepared in situ in differential scanning calorimetry by quenching the melted physical mixtures of sulfamethazine and each impurity compound in the differential scanning calorimetry pan. In the following heating process, the glass transition temperatures (Tg) of each were measured. The fragility parameters were estimated from the width of Tg. The Tg of amorphous sulfamethazine with those impurities changed in accordance with the manner set forth in the Gordon-Taylor equation. The fragility parameter slightly increased when a small amount of SNA or SMR was incorporated. Moreover, the probability of a measurement in which crystallization of sulfamethazine was observed above its Tg, increased at a low-concentration range of SNA, SMR, or sulfadimethoxine. It was considered that the existence of a small amount of impurity would induce heterogeneity in the molecular density of the amorphous state, which would be associated with the local fluctuation. It was suggested that the change in the molecular dynamics would be related to the probability of crystallization of sulfamethazine.


Subject(s)
Drug Contamination , Molecular Dynamics Simulation , Sulfamethazine/chemistry , Sulfonamides/chemistry , Transition Temperature , Differential Thermal Analysis/methods , Sulfamethazine/analysis , Sulfonamides/analysis
13.
São Paulo; s.n; s.n; 2017. 124 p. tab, ilus, graf.
Thesis in Portuguese | LILACS | ID: biblio-875323

ABSTRACT

O presente trabalho teve como objetivo o estudo do estado sólido do ganciclovir (GCV) e suas diferentes formas polimórficas. O GCV é um fármaco antiviral útil no tratamento de infecções por citomegalovírus (CMV). Embora seja um fármaco amplamente usado, poucos estudos têm sido realizados sobre seu estado sólido. Atualmente, o GCV é conhecido por apresentar quatro formas cristalinas, duas anidras (Forma I e II) e duas hidratas (III e IV). Neste trabalho, nós reportamos a solução da estrutura cristalográfica da Forma I do GCV, que foi encontrado durante o screening de cristalização do fármaco, em que nove ensaios de cristalização (GCV-1, GCV-A, GCV-B, GCV-C, GCV-D, GCV-E, GCV-F, GCV-G e GCV-H) foram realizados e os materiais resultantes foram caracterizados por Difratometria de raios X (DRX), análise térmica (DTA/TG) e Hot Stage Microscopy. De todas as cristalizações realizadas foram obtidas quatro formas sólidas, denominadas como Forma I (GCV-1, GCV-B e GCV-H), Forma III (GCV-C, GCV-D, GCV-F e GCV-G), Forma IV (GCV-A) e Forma V (GCV-E). Esta última está sendo descrita pela primeira vez na literatura e indica a presença de outra forma hidratada de GCV. As Formas I, III e IV corresponderam a forma anidra e as duas formas hidratadas do fármaco, respectivamente. Além disso, foi evidenciado por experimentos de conversão de slurry e análise térmica que o cristalizado de GCV-1 (Forma I) foi o mais estável entre os materiais obtidos, e este deu origem ao monocristal da Forma I de GCV, estrutura cristalina anidra do fármaco. Neste trabalho, pela primeira vez, a estrutura cristalina deste composto foi definida por cristalografia de raios X de monocristal. A análise estrutural mostrou que a Forma I do fármaco cristaliza no grupo espacial monoclínico P21/c e está composta por quatro moléculas de GCV na sua unidade assimétrica. Cada molécula está unida intermolecularmente por ligações de hidrogênio, que dão lugar à formação de cadeias infinitas e estas por sua vez se arranjam de maneira a formar uma estrutura tridimensional.


This presented work aims to study the solid state of ganciclovir (GCV) and its different polymorphic forms. GCV is an antiviral drug useful in the treatment of cytomegalovirus (CMV) infections. Although it is a widely-used drug, few studies have been conducted on its solid state. Currently, GCV is known to have four crystalline forms, two anhydrous (Form I and II) and two hydrates (III and IV). In this investigation, we report a successful preparation of GCV Form I and its crystallographic structure, which was found during the crystallization of the drug, in which nine crystallization tests (GCV-1, GCV-A, GCV-B, GCV- D, GCV-E, GCV-F, GCV-G and GCV-H) were performed and the resulting materials were characterized by X-ray diffractometry (XRD), thermal analysis (DTA/TG) and Hot Stage Microscopy. Of all the crystallizations performed, four solid forms were obtained, denoted as Form I (GCV-1, GCV-B and GCV- H), Form III (GCV-C, GCV-D, GCV-F and GCV-G), Form IV (GCV-A) and Form V (GCV-E). The latter is being described for the first time in the literature and indicates the presence of another hydrated form of GCV. Forms I, III and IV corresponded to the anhydrous form and the two hydrated forms of the drug, respectively. In addition, it was evident by both the slurry conversion and the thermal analysis methods that the GCV-1 crystallized (Form I) was indeed the most stable amongst the materials obtained. This gave rise to GCV Form I monocrystal, anhydrous crystalline structure of the drug. The compound was characterized by monocrystal X-ray crystallography. The structural analysis showed that Form I of the drug crystallized in the monoclinic system space group P21/c is composed of four molecules of GCV in its asymmetric unit. Each molecule is linked intermolecularly by hydrogen bonds, which give rise to the formation of infinite chains arranged in a way that form a three-dimensional structure.


Subject(s)
Ganciclovir/analysis , Crystallization , Ganciclovir/chemistry , Differential Thermal Analysis/methods
14.
Org Biomol Chem ; 14(30): 7238-49, 2016 Jul 26.
Article in English | MEDLINE | ID: mdl-27383473

ABSTRACT

We report on the potential of a water-soluble tetracationic quaternary ammonium naphthalene diimide (NDI) as multifunctional agent of interest for theranostic applications. The DNA binding ability of this NDI has been investigated. NDI exhibits high binding constants for G-quadruplex DNA but it is not selective for this type of DNA. Taking advantage of its intrinsic fluorescence and singlet oxygen sensitizing ability, cellular uptake, cytotoxicity and photocytotoxicity have been investigated. The intense emission in the red/NIR allows monitoring of the cell permeability of this charged tetracationic NDI, accumulating into the cell nuclei. No dark cytotoxicity has been observed on selected tumor cell lines. Irradiation of the NDI loaded cells with red light reduces cell viability up to 40% and causes a significant increase of the percentage of cells expressing γH2AX foci indicating DNA damage. The presence of distinct DNA damage foci inside the nucleus suggests that the NDI molecule might induce DNA damage in specific sites. To the best of our knowledge this is the first NDI exhibiting PDT activity at µM concentration combined with low dark cytotoxicity.


Subject(s)
Fluorescent Dyes/chemistry , Fluorescent Dyes/toxicity , Imides/chemistry , Imides/toxicity , Naphthalenes/chemistry , Naphthalenes/toxicity , Theranostic Nanomedicine/methods , Biological Transport , Cell Line, Tumor , Cell Survival , Differential Thermal Analysis/methods , Fluorescent Dyes/metabolism , G-Quadruplexes , Humans , Imides/metabolism , Molecular Structure , Naphthalenes/metabolism , Optical Imaging , Photochemical Processes , Singlet Oxygen/chemistry , Structure-Activity Relationship , Thermodynamics
15.
J Food Sci ; 80(2): C218-27, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25588413

ABSTRACT

Volatiles from initially frozen, dense phase carbon dioxide (DPCD)- and thermally treated guava purees were isolated by solid phase microextraction (SPME), chromatographically separated and identified using a combination of gas chromatography-mass spectrometry (GC-MS), GC-olfactometry (GC-O), and GC-pulsed flame photometric detector (GC-PFPD, sulfur mode). Fifty-eight volatiles were identified using GC-MS consisting of: 6 aldehydes, 2 acids, 15 alcohols, 6 ketones, 21 esters, and 8 terpenes. Eleven volatiles were newly identified in guava puree. Hexanal was the most abundant volatile in all 3 types of guava puree. Ten sulfur compounds were identified using GC-PFPD of which 3 possessed aroma activity and 3 were not previously reported in guava puree. Both treatments profoundly reduced total sulfur peak areas and produced different peak patterns compared to control. Thermal treatment reduced total sulfur peak area 47.9% compared to a loss of 34.7% with DPCD treatment. Twenty-six volatiles possessed aroma activity. (Z)-3-Hexenyl hexanoate was the major contributor to the aroma of the freshly thawed and DPCD-treated guava puree. DPCD treatment reduced total MS ion chromatogram (MS TIC) peak area 35% but produced a GC-O aroma profile very similar to control. Whereas thermal treatment reduced total TIC peak area only 8.7% compared to control but produced a 35% loss in total GC-O peak intensities.


Subject(s)
Differential Thermal Analysis/methods , Food Handling/methods , Odorants/analysis , Psidium/chemistry , Sulfur Compounds/isolation & purification , Volatile Organic Compounds/isolation & purification , Acids/analysis , Alcohols/analysis , Aldehydes/analysis , Carbon Dioxide , Esters/analysis , Gas Chromatography-Mass Spectrometry/methods , Ketones/analysis , Solid Phase Microextraction/methods , Sulfur/analysis , Terpenes/analysis
16.
Expert Rev Anti Infect Ther ; 13(1): 119-29, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25488142

ABSTRACT

INTRODUCTION: Drugs classified as class IV by the Biopharmaceutical Classification System present significant problems in relation to effective oral administration. In the case of antibiotics, the subsequently high doses required can enhance the emergence of microorganism resistance and lead to a low rate of patient treatment adherence. OBJECTIVE: In an attempt to improve physicochemical properties and microbiological activity of norfloxacin, the aim of this study was to investigate different methods (coevaporation, kneading followed by freeze-drying or spray-drying) to obtain complexes of norfloxacin and different cyclodextrins. METHODS: Guest-host interactions were investigated through a complete physical-chemical characterization and the dissolution profile and microbiological activity were determined. RESULTS: The formation of a complex of norfloxacin and ß-cyclodextrin (1:1), obtained by kneading followed by freeze drying, led to increased drug solubility, which could maximize the oral drug absorption. CONCLUSION: Moreover, the microbiological activity was enhanced by around 23.3%, demonstrating that the complex formed could represent an efficient drug delivery system.


Subject(s)
Anti-Bacterial Agents/chemistry , Drug Carriers , Norfloxacin/chemistry , beta-Cyclodextrins/chemistry , Anti-Bacterial Agents/pharmacology , Differential Thermal Analysis/methods , Drug Stability , Microscopy, Electron, Scanning/methods , Norfloxacin/pharmacology , Pharmaceutical Preparations , Potentiometry/methods , Powder Diffraction , Solubility , Spectroscopy, Fourier Transform Infrared/methods , Staphylococcus epidermidis/drug effects
17.
Expert Rev Anti Infect Ther ; 13(1): 131-40, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25488143

ABSTRACT

INTRODUCTION: Norfloxacin (NFX) is a broad spectrum antibiotic with low solubility and permeability, which is unstable on exposure to light and humidity. OBJECTIVE: In this study, the mode of NFX inclusion into ß-cyclodextrin complexes was evaluated and a complete physical, chemical and microbiological stability study of the inclusion complexes was carried out. METHODS: Potentiometric titrations were performed to evaluate changes in the pKa of the NFX molecule due to the formation of an inclusion complex and NMR analysis demonstrated that the NFX molecule is included in the ß-cyclodextrin cavity. RESULTS: Inclusion complexes obtained by kneading followed by freeze-drying showed improved NFX stability compared with the isolated drug or the physical mixture. This method was effective in terms of protecting the drug from photodegradation and also avoiding hydrolysis. Differences between NFX and the complexes could be evidenced by thermal analysis, infrared spectroscopy and x-ray powder diffraction as well as by determining the solubility and drug content. The antimicrobial potency was also preserved on applying the promising method of kneading. CONCLUSION: The satisfactory stability indicates that the NFX/ß-cyclodextrin complexes could be useful as an alternative to the existing NFX drug formulation.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Delivery Systems/methods , Norfloxacin/pharmacology , Technology, Pharmaceutical/methods , beta-Cyclodextrins/pharmacology , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacokinetics , Differential Thermal Analysis/methods , Drug Resistance, Bacterial , Drug Stability , Microscopy, Electron, Scanning/methods , Norfloxacin/analysis , Norfloxacin/chemistry , Norfloxacin/pharmacokinetics , Pharmaceutical Preparations/chemical synthesis , Potentiometry/methods , Powder Diffraction , Solubility , Spectroscopy, Fourier Transform Infrared/methods , Staphylococcus epidermidis/drug effects , beta-Cyclodextrins/analysis , beta-Cyclodextrins/chemistry , beta-Cyclodextrins/pharmacokinetics
18.
Zhongguo Zhong Yao Za Zhi ; 40(16): 3245-8, 2015 Aug.
Article in Chinese | MEDLINE | ID: mdl-26790301

ABSTRACT

Crystal structures of chemical drugs has been being investigated widely. But few attention has been paid to polymorphs-phenomena of active ingredients from Traditional Chinese Medicine(TCM). Taking anhydrous dehydroandrographolide and hydrousprim-O-glucosylcimifugin as example, differences between TCM reference substances (RSs) with different crystal structures were discussed by using microscopy, melting point determination, differential thermal analysis (DTA) and infrared (IR) methods. The results showed that different crystal structures could lead to change of melting points, thermal behaviors and IR spectrum. It's indicated that polymorphs may be considered if different physicochemical properties were obtained when applying TCM RS. Differences of chemical properties of active ingredients from TCM with different crystal structures need further investigation.


Subject(s)
Differential Thermal Analysis/standards , Drugs, Chinese Herbal/chemistry , Spectrophotometry, Infrared/standards , Crystallization , Differential Thermal Analysis/methods , Drugs, Chinese Herbal/standards , Medicine, Chinese Traditional , Molecular Structure , Reference Standards , Spectrophotometry, Infrared/methods , Transition Temperature
19.
Methods Mol Biol ; 1166: 91-8, 2014.
Article in English | MEDLINE | ID: mdl-24852631

ABSTRACT

Infrared thermal analysis is an invaluable technique to study the plant freezing process. In the differential mode infrared thermal analysis allows to localize ice nucleation and ice propagation in whole plants or plant samples at the tissue level. Ice barriers can be visualized, and supercooling of cells, tissues, and organs can be monitored. Places where ice masses are accommodated in the apoplast can be identified. Here, we describe an experimental setting developed in the laboratory in Innsbruck, give detailed information on the practical procedure and preconditions, and give additionally an idea of the problems that can be encountered and how they by special precautions may be overcome.


Subject(s)
Differential Thermal Analysis/methods , Freezing , Infrared Rays , Senecio/chemistry , Ice
20.
Article in English | MEDLINE | ID: mdl-24727178

ABSTRACT

The characterization of archeological ceramic and pottery can be studied for the determination of firing temperature and the presence of raw materials by thermal analysis. Clay minerals are the main material for the production of ceramic and pottery and show some characteristic reactions such as dehydration, dehydroxylation and transformation. This is key point of criteria for the elucidation of firing temperature and raw material analysis. In the present work, DTA-TG, XRD and EDXRF technique are applied on representative potsherds from Vellore dist., Tamilnadu, India to derive the information about the production technology, raw materials and firing temperature. From the analysis, all the samples were considered to be fired from 800°C to 900°C and organic material might be added intestinally as a binder in the preparation of pottery.


Subject(s)
Ceramics/chemistry , Ceramics/history , Differential Thermal Analysis/methods , Thermogravimetry/methods , Aluminum Silicates/chemistry , Aluminum Silicates/history , Archaeology/history , Archaeology/methods , Clay , History, Ancient , Hot Temperature , India , Powder Diffraction , X-Ray Diffraction
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